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PubMed1977

Concept of paraneurons.

Paraneurons are those cells which have not been designated as neurons but are recognized as closely related to neurons on the basis of their fine structure (possession of neurosecretion-like and synaptic vesicle-like granules/vacuoles), metabolism (production of neurosecretion- and neurotransmitter-like substances) and origin (evidenced or proposed neuroectodermal). Some paraneurons are mainly endocrine in function, while others are sensory. Some should be called interneurons. There are graduations between these types of paraneurons; also a definite boundary between neurons and paraneurons can not be determined. Different types of paraneurons (together with some related neurons) are shown in Figure 1. Comments and discussions were given on the neuron-like characteristics of the individual paraneurons.

APUD Cells↗
PubMed1995

The role of 111In-octreotide scintigraphy in the detection of APUD tumours: our experience in eighteen patients.

111In-Octreotide scintigraphy has been recently proposed as a sensitive technique for the detection of neuroendocrine tumours, based on the high radiotracer affinity towards the somatostatin receptors expressed by the APUD-system cells. In the present study, a group of 18 patients with carcinoid tumours and gastrointestinal (GI) apudomas was investigated to assess the accuracy of Octreotide scintigraphy in localizing primitive, recurrent or metastatic lesions. Both planar and SPECT studies were obtained 4 hours after the i.v. injection of 111In-Octreotide (111 MBq); planar images were also carried out 24 hours later. In accordance with other authors, the sensitivity of the method was found to be very high (94%) in our group of patients; only in one case of nesidioblastosis was the scintigraphy negative. No differences in sensitivity were observed between the planar and SPECT studies, but the latter provided a better topographic localization of the neoplastic foci. It should be pointed out that in 7 cases (3 primitive, 1 recurrent and 3 metastatic lesions) scintigraphy correctly localized the tumour, when the other morphological techniques, such as echography, computed tomography or magnetic resonance, failed. On the basis of our data, we believe that Octreotide scintigraphy should be the first study performed in the evaluation of patients affected by APUD tumours.

Angiography↗
PubMed1990

Intermediate filament expression in pituitary adenomas.

Seventy-five formalin-fixed and 18 alcohol-fixed pituitary adenomas were studied immunohistochemically using antibodies to keratin, vimentin, neurofilaments (NFs), glial fibrillary acidic protein, desmin, actin, S-100 protein and a variety of pituitary hormones. The pituitary adenoma cells were positive for keratin, vimentin and NFs (68 kDa and 160 kDa) and in a few instances there was co-expression of these three types of intermediate filaments (IMFs). The pattern of keratin-specific staining showed diffuse cytoplasmic or patchy paranuclear reactivity and of NF- or vimentin-specific staining showed fibrillar or patchy paranuclear reactivity. The patchy staining seemed to decorate the fibrous body. There was no correlation between the distribution of IMFs and pituitary hormones in pituitary adenomas except that melanocyte-stimulating-hormone-positive reactivity was limited to the NF-positive adenomas. The pattern of IMF staining did not depend on hormone production in adenomas.

APUD Cells↗
PubMed1997

An immunohistochemical study of the endocrine cells within the pancreas, intestine, and stomach of the gar (Lepisosteus osseus L.)

The distribution and identity of the various endocrine cell types were examined in the pancreas, stomach, and anterior intestine of the phylogenetically ancient actinopterygian, the gar (Lepisosteus osseus L.), using immunohistochemistry. Antisera used were directed against several insulins (INSs) and somatostatins (SSTs), and members of the pancreatic polypeptide (PP, aPY, NPY) and glucagon (GLUC, GLP) families. In the gar pancreas the most pronounced aggregation of islet tissue is among the exocrine acini near the union of extrahepatic common bile duct with the gastrointestinal junction. Four immunoreactive cell types were identified within well-defined islets (A, B, D, and F cells) but immunoreactive cell types were also seen isolated among the exocrine acini. Centrally located B cells were immunoreactive with mammalian and lamprey INS antisera whereas the widely dispersed D cells immunostained with anti-SST-14, -25, and -34. SST was also localized in the epithelium of the pancreatic ducts. There was a colocalization of immunoreactivity for each member of the PP and GLU families at the periphery of each islet to identify F and A cells, respectively. However, colocalization of peptides from both families is suspected for at least some cells. Although the gastric and intestinal mucosae showed a similar pattern of immunoreactivity to GLP and not GLU, they had contrasting immunoreactivity with the two INS antisera. SST immunoreactivity was restricted to the stomach, whereas three of the four PP-family peptides were only immunoreactive in the intestine. Immunoreactivity to the various antisera used in the study imply that there may be an organ-specific processing of preproinsulin, that the gar SST profile may be more similar to agnathan and bowfin rather than either elasmobranch or teleost SSTs, and that only the GLP portion of the preproglucagon gene is expressed in the gastrointestinal mucosa. Our results are consistent with other recent endocrine studies showing that the gar is a widely distinct actinopterygian.

APUD Cells↗
PubMed1991

Investigation on serum neurone-specific enolase in prostate cancer diagnosis and monitoring: comparative study of a multiple tumor marker assay.

A quadruple tumor marker serotest assay (neurone-specific enolase, NSE, prostate-specific antigen, PSA, prostatic acid phosphatase, PAP, and carcino-embryonic antigen, CEA) was performed on sera from both 63 patients with untreated prostate cancer and 135 patients treated with orchiectomy, flutamide, diethylstilbestrol (DES), cyproterone acetate (CPA), and Estracyt. In untreated patients with local tumor elevated blood NSE concentrations were found more frequently (10/35, 28.6%) than in untreated subjects with disseminated disease (3/28, 10.7%). Elevated NSE values were measured more frequently in nonresponders to therapy 10/46 (21.7%), than in responders during prostate cancer partial remission (2/89, 2.2%). In none of NSE-positive neoplasms a small cell prostate cancer has been histologically detected. Many of NSE-positive tumors are also closely associated with elevated blood CEA values. The applied anticancer drugs were inefficient in the normalization of neither one from the pair of elevated NSE and CEA concentrations (regardless of the numerical values of the other two markers, PSA and PAP), but their values were found to decline occasionally only after surgical treatment. In patients with raised PSA, PAP, and CEA levels but with a normal NSE value, the application of the same treatment strategies was in the most of subjects sufficient to provoke either temporary or even lasting tumor response to therapy. Hence, it appears that the assessment of the NSE serotest, despite its minimal value in the overall tumor staging and monitoring, might furnish the decision-making step related to the treatment of aggressive prostate cancer with an additional and powerful tool.

APUD Cells↗
PubMed1991

Effects of a long-standing challenge on pulmonary neuroendocrine cells of actively sensitized guinea pigs.

Histologic studies using the silver stain method have implicated pulmonary neuroendocrine cells (NEC) in asthma by demonstrating an increase in their number in the bronchi of guinea pigs actively sensitized with ovalbumin and 10 min after challenge. We verified the same data and completed them by a study of the long-standing effects of a challenge on NEC number in guinea pig bronchi. Actively sensitized animals were killed 2, 6, 24, 48, 72, and 144 h after being challenged by an aerosolized solution of ovalbumin. This study was completed by the evaluation of eosinophilic infiltration of bronchi to test the recently proposed hypothesis of the possible eosinophil recruitment by NEC product. Our results confirmed the increase in NEC number in the bronchial wall after sensitization. Originally we demonstrated that, 24 h after challenge, the NEC number decreased significantly, compared to sensitized only animals, suggesting possible product release. Eosinophilic migration was observed in sensitized animals and, more importantly, in all sensitized plus challenged animals. We suggest that bronchial NEC may play a role in immunoallergic events that take place in the lung after challenge, probably by releasing mediators that may influence, among other effects, eosinophilic recruitment.

APUD Cells↗
PubMed1985

Serotonin and carcinoid tumors.

The enterochromaffin (EC) cell system is distributed throughout the entire gastrointestinal tract. Enterochromaffin cells are the major source of intestinal serotonin (5-HT), but separate subpopulations of EC cells may synthesize and store peptides as substance P (SP), motilin, and enkephalin as well. Of special interest is that 5-HT and SP, which may coexist in EC cells, have several functional similarities, i.e., inhibition of gastric acid secretion, stimulation of intestinal motility, and secretion of water and electrolytes. Carcinoid tumors are derived from the gut endocrine system. Depending on site of origin, carcinoids are divided into foregut, midgut, and hindgut derivatives with different clinical symptoms. A common biochemical feature of midgut carcinoids is the production of 5-HT and SP. Histochemically, midgut carcinoids are characterized by the argentaffin reaction--a direct reduction of silver salts owing to 5-HT. Specific antisera for the immunocytochemical demonstration of secretory products are available as well. Despite their relative infrequency, carcinoids are the most common small intestinal tumors. The common appendix tumors generally have a benign clinical course, whereas the small intestinal tumors have different growth patterns and frequently metastasize with increasing size, and may thus give rise to the carcinoid syndrome (diarrhea, facial flush, right-sided cardiac valvular disease, and asthma). Carcinoid symptoms first appear when hepatic inactivation of 5-HT is exceeded, unless the carcinoid has an extraintestinal localization, for example, ovarian lesions may elicit symptoms in the absence of hepatic disease owing to direct secretion into systemic circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

APUD Cells↗
PubMed1992

Modulation of the incidence of hamster pulmonary endocrine cell hyperplasia by unilateral collapse of the lung.

We evaluated the effects of the unilateral collapse of the left lung on the formation of pulmonary endocrine cell hyperplasia (PECH) induced by 4-nitroquinoline 1-oxide (4NQO) in Syrian golden hamsters. Ten hamsters were injected subcutaneously with 20 mg/kg body weight of 4NQO, once a week for 4 weeks and treated with injection of silicone rubber into the left thorax at the 8th experimental week. Another 30 animals were divided into three groups: treated with 4NQO only, left lung collapse only, and vehicle only. All animals were sacrificed at the 30th week. The lung tissues were embedded in paraffin; 50 serial sections were made from the tissues of each animal and were studied histologically and immunohistochemically. PECH showed a positive immunostain for calcitonin and/or serotonin. In the uncollapsed right lungs of the animals treated with both 4NQO and unilateral collapse, the mean incidence of PECH was 12.2 x 10(-2)/mm3 lung volume; the incidences of PECH in the animals treated with 4NQO only, collapse only, and vehicle only were 4.1, 3.8, and 1.4 x 10(-2)/mm3, respectively. In the collapsed left lungs, PECH did not form, regardless of 4NQO treatment. This study demonstrates that unilateral collapse of the lung modulates the incidence of PECH induced by 4NQO in hamsters.

4-Nitroquinoline-1-oxide↗
PubMed1997

Pulmonary endocrine cell hyperplasia and papilloma in rats induced by intratracheal injections of extract from particulate air pollutants.

We investigated the effect of intratracheal injections of an extract of suspended particulate matter (SPM) obtained from the urban ambient air of Tokyo, upon the development of proliferative lesions of pulmonary endocrine cells (PECs) in the rat. We also examined the modification effects of nitrogen dioxide, sulfur dioxide, or both of them on the PEC lesions. Male F344 rats were divided into six experimental groups of 5 animals each. Twenty animals were treated with intratracheal instillations of SPM admixed with carbon once a week for 4 weeks with or without additional gaseous exposure (6 ppm nitrogen dioxide or 4 ppm sulfur dioxide) 16 hrs a day for 11 months. Five animals were given intratracheal injections of carbon suspended in saline and the other five were untreated. The subcardiac lobes of the right lung were fixed with 4% paraformaldehyde, and embedded in paraffin. PEC hyperplasias and papillomas were counted in 200 serial sections, 4 microns thick. The average incidences of PEC hyperplasia in the untreated animals and in those treated with carbon were 194 and 200/cm3, respectively. The average incidences of PEC hyperplasia in the animals exposed to SPM tar only, SPM tar plus nitrogen dioxide and sulfur dioxide, SPM tar with nitrogen dioxide and SPM tar with sulfur dioxide were 376, 378, 372 and 349/cm3, respectively. These were significantly higher than the levels of the control animals, and additional gaseous stimuli had no effect on the incidence of PEC hyperplasia. Besides PEC hyperplasia, a few PEC papillomas were found in the animals treated with SPM tar, regardless of gaseous exposure, but in the control animals no papilloma was evident. Thus, compounds in airborne particulates are considered to be responsible for the development of PEC hyperplasias and papillomas.

APUD Cells↗
PubMed1976

Carcinoid of the uterine cervix: additional observations on a new tumor entity.

Twelve carcinoid tumors of the uterine cervix were studied. Based on the microscopic structure, they were divided into well-differentiated and poorly differentiated types. Both tumor varieties affected adult women. The clinical and gross features of these tumors were indistinguishable from those of invasive squamous cell carcinoma. Of the 12 patients, six died, four with poorly differentiated carcinoid and two with the well-differentiated type. Three patients are alive and symptom-free 9 months to 2 years after treatment; the remaining three were lost to follow-up. Microscopically, four well-differentiated carcinoids showed argyrophil cells, and ultrastructurally two had neurosecretory granules. One of the well-differentiated carcinoids resembled islet cell carcinoma and two had areas resembling medullary carcinoma of the thyroid. The poorly differentiated type of carcinoid had a histologic structure and a cell population very similar to that of the oat cell carcinoma of the lung. Of this group, four were argyrophilic, and by electron microscopy four contained pleomorphic secretory granules. It is considered that these tumors arise from the normal argyrophil cell of the cervix and are part of the group of neoplasms of the diffuse endocrine cell system (APUD).

Adult↗
PubMedDate not supplied

Pathology of APUDomas.

The pathology of APUDomas involves two main areas. The first is the biochemical aspects of these tumours and the use of biochemical tests to investigate a patient suspected of having an APUDoma, and the other is the histopathology of these tumours. This review is devoted to the histopathological considerations.

APUD Cells↗
PubMedDate not supplied

Central and autonomic nervous system links to the APUD system (and their APUDomas).

The concept of the APUD system and the APUDomas associated with it has evolved significantly since Pearse's description in the 1960s. Part of this evolution has been an understanding of the relationships between the APUD system and the central and autonomic nervous systems. The APUD system now referred to as the diffuse neuroendocrine system, can be linked to the central nervous system and autonomic nervous system by genetics, embryology, cellular characteristics, anatomy, interaction of the systems, and the immune system. Awareness of these relationships may enable clinicians to better understand APUDomas and lead to better methods of detection of these tumours and their treatment.

APUD Cells↗
PubMed1982

Ectopic hormones.

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APUD Cells↗
PubMed1980

Histochemical analysis of senile plaque amyloid and amyloid angiopathy.

Histochemical methods were used to obtain information on the chemical constituents of brain amyloid in senile dementia of the Alzheimer type. The staining properties of brain amyloid (senile plaque and amyloid angiopathy) were compared with those of extraneural amyloidosis and endocrine amyloid. We found no histochemical differences between amyloid in senile plaques and in amyloid angiopathy. The content of aromatic amino acids was higher in amyloid of plaques and in amyloid angiopathy than in endocrine amyloid. Furthermore, we found persistent birefringence and affinity of brain amyloid for Congo red after exposure to potassium permanganate, suggesting that AA amyloid is not a major constituent of cerebral amyloid.

APUD Cells↗